Taking a low dose of aspirin every day may halve the risk of developing pancreatic cancer, according to one of the largest studies into the drug's anti-cancer effects.

US researchers found that people who took low-dose aspirin regularly for several years – often to prevent cardiovascular disease – had a substantially lower risk of being diagnosed with the cancer.

Doctors at Yale University said that people who took low-dose aspirin for three years before their study began had a 48% lower risk of pancreatic cancer, while those who started taking the drug 20 years before the study had a 60% lower risk.

"Using low-dose aspirin seems to cut the risk of pancreatic cancer by half," said Harvey Risch, professor of epidemiology at Yale University in Connecticut. "We saw significant reductions in risk with short-term usage as well as with long-term usage."

The study builds on a body of work that suggests one of the cheapest and most common drugs on the market could help to protect against certain types of cancer. But while there is good evidence that aspirin prevents some forms of the disease, such as bowel cancer, the evidence is weaker for others, pancreatic cancer included. A large study of women in 2004 found that aspirin might actually increase their risk of pancreatic cancer.

Given the uncertainties, doctors say healthy people should not take aspirin to protect against cancer unless they know they are in a high-risk group, because the potential side-effects may outweigh any benefits. Aspirin makes blood platelets less sticky and so less able to clot in the bloodstream. While that can reduce the risk of heart attacks and strokes caused by blood clots, it can make burst blood vessels in the brain more dangerous, and raises the risk of stomach bleeds, which on rare occasions are fatal.

"This is something that has pros and cons and GPs should be able to help patients to figure out the magnitude of the risks in either direction," Risch told the Guardian. "Aspirin is not totally harmless. It has its own side-effects. But if somebody's doctor said they had a high risk of pancreatic cancer because of a family history, I'd say low dose aspirin is a reasonable thing to use as part of a risk-reduction plan."

The researchers interviewed 690 healthy controls and 362 patients newly diagnosed with pancreatic cancer at 30 general hospitals in Connecticut between 2005 and 2009. Each was asked whether they had taken aspirin, at what dose, and when. A "low dose" meant 75mg to 325mg of aspirin, and was usually taken once a day to prevent cardiovascular disease. Higher doses of aspirin were considered "regular doses" and were often taken four times a day for pain relief. In the study, around 57% of the participants were men, half smoked, or used to smoke, and a fifth had diabetes.

Asking people to remember what pills they took and when is not the most reliable way of recording people's medical history, but Risch believes that his findings would not be undone by mistaken recall.

The study, published in the journal Cancer Epidemiology, Biomarkers and Prevention, raises questions about how aspirin might prevent cancer. Risch said one idea was that aspirin hit newly formed cancerous cells, but the study found that people who took the drug for three to five years were protected nearly as much as those who took it for 20 years.

The first pancreatic cancer cells can start to grow in the body 15 years before a person is diagnosed with the disease. Though the details are unclear, aspirin might work in several ways: by reducing inflammation, slowing mutations in cells, and preventing cancer cells being spread around the body on blood platelets.

Last week, researchers led by Colin McCowan at Glasgow University published a report in the British Journal of Cancer that found low-dose aspirin may nearly halve the risk of death in women diagnosed with breast cancer.

"There is a growing body of evidence that low-dose aspirin use may be effective in reducing different cancers, including pancreatic cancer as studied in this work. However, the current evidence is mainly from observational studies so there is still a possibility that it is not aspirin use but rather something about people who take aspirin that means they are less likely to develop cancers," McCowan said.

"Taking aspirin can cause problems for some patients – it can increase the risk of internal bleeding leading to serious complications and death – so no-one should start taking it without consulting their doctor."

Julie Sharp at Cancer Research UK said: "Aspirin is showing promise in preventing certain types of cancer – notably bowel cancer – and this study provides tentative evidence that it could have a role against pancreatic cancer, although larger, prospective studies are needed to confirm this. But aspirin can cause complications such as bleeding and stomach ulcers in some people and we need to find ways to predict who should take aspirin, how much should be taken and how long for, before it can be recommended for widespread use in preventing cancer."